tbuckley/cabot-search huggingface dataset:
Focal Adhesion Kinase as a Therapeutic Target for Meningiomas With Somatic Neurofibromatosis Type 2 Mutations
Authors: Warren P. Mason
Journal: Journal of Clinical Oncology (2022)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations. October 26, 2022 ARTICLE CITATION DOI: 10.1200/JCO.22.01914 Journal of Clinical Oncology - published online before print October 26, 2022 PMID: 36288506 Focal Adhesion Kinase as a Therapeutic Target for Meningiomas With Somatic Neurofibromatosis Type 2 Mutations Warren P. Mason , MD1xWarren P. MasonSearch for articles by this author Show More 1Princess Margaret Cancer Centre, Toronto, ON, Canada https://doi.org/10.1200/JCO.22.01914 First Page Full Text PDF Figures and Tables © 2022 by American Society of Clinical OncologyAUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTFocal Adhesion Kinase as a Therapeutic Target for Meningiomas With Somatic Neurofibromatosis Type 2 MutationsThe following represents disclosure information provided by the author of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Warren P. MasonHonoraria: Bayer, Viatris, Inc, Apotex, Inc, GlaxoSmithKlineExpert Testimony: MedcanNo other potential conflicts of interest were reported. Companion Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations
Stress Relaxation‐Induced Colon Tumor Multicellular Spheroid Culture Based on Biomimetic Hydrogel for Nanoenzyme Ferroptosis Sensitization Evaluation
Authors: Yi Zhang, Liyi Peng, Ke Hu, Ning Gu
Journal: Advanced Healthcare Materials (2022)

Ferroptosis has recently become a research hotspot, and the induction of tumor cell ferroptosis has emerged as a powerful method for tumor therapy. However, the efficiency of tumor cell ferroptosis induction remains unmet for clinical use, which may be attributed to the large discrepancies between in vitro and in vivo models. To address this issue, in this study, a hydrogel platform with stress relaxation is utilized to develop a multicellular spheroid model of the DLD1 colon cancer cell line through cancer cell self-organization. The spheroids are highly similar to real tumor tissue, and ferroptosis resistance at the transcriptional, protein, and cellular levels. Collaboration of the ferroptosis induction reagent erastin and the nanoenzyme MnZnFe2 O4 @PEG-COOH to overcome the ferroptosis resistance of the spheroids is also demonstrated. Taken together, this study demonstrates the effectiveness of the model developed using this hydrogel platform for further mechanistic studies, and for the assessment of novel cancer treatment strategies based on ferroptosis.
Advances in the Translation of Electrochemical Hydrogel‐Based Sensors
Authors: Houda Shafique, Justin de Vries, Julia Strauss, Arash Khorrami Jahromi, Roozbeh Siavash Moakhar, Sara Mahshid
Journal: Advanced Healthcare Materials (2022)

Novel biomaterials for bio- and chemical sensing applications have gained considerable traction in the diagnostic community with rising trends of using biocompatible and lowly cytotoxic material. Hydrogel-based electrochemical sensors have become a promising candidate for their swellable, nano-/microporous, and aqueous 3D structures capable of immobilizing catalytic enzymes, electroactive species, whole cells, and complex tissue models, while maintaining tunable mechanical properties in wearable and implantable applications. With advances in highly controllable fabrication and processability of these novel biomaterials, the possibility of bio-nanocomposite hydrogel-based electrochemical sensing presents a paradigm shift in the development of biocompatible, "smart," and sensitive health monitoring point-of-care devices. Here, recent advances in electrochemical hydrogels for the detection of biomarkers in vitro, in situ, and in vivo are briefly reviewed to demonstrate their applicability in ideal conditions, in complex cellular environments, and in live animal models, respectively, to provide a comprehensive assessment of whether these biomaterials are ready for point-of-care translation and biointegration. Sensors based on conductive and nonconductive polymers are presented, with highlights of nano-/microstructured electrodes that provide enhanced sensitivity and selectivity in biocompatible matrices. An outlook on current challenges that shall be addressed for the realization of truly continuous real-time sensing platforms is also presented.
Hyoepiglottic Rheumatoid Nodule Mimicking Head and Neck Malignancy on 18F-FDG PET/CT
Authors: Ludwig Opalinski, Sandra Schmitz, Pascal Van Eeckhout, Philippe d’Abadie, Olivier Gheysens
Journal: Clinical Nuclear Medicine (2022)

A 54-year-old man with a history of tonsillar squamous cell carcinoma treated with chemoradiotherapy and an 18-year history of seropositive rheumatoid arthritis in remission without maintenance therapy presented with right cervical pain and dysphagia for several months. Flexible laryngoscopy did not show any lesion, and MRI revealed a necrotic lesion inside the thyro-hyo-epiglottic space attached to the hyoid bone. 18 F-FDG PET/CT demonstrated a moderately increased metabolic activity of the lesion without any other suspected lesions. Surgical resection was performed, and pathology revealed a necrotizing granuloma compatible with a rheumatoid nodule.
An observational investigation of the faecal microbiota and metabonome of gastrostomy fed children, on blended and formula diets
Authors: Julian R. Marchesi, Sophie Allen, Emma Scott, Huw Jenkins, Claire Sadlier, Sian Thomas
Journal: Gut Microbes (2022)

Gastrostomy fed children traditionally have a Formulae diet (FD), which fulfills nutritional requirements; however, many families are adopting Blended diets (BD), which are what the whole family would eat. We undertook an observational investigation of the colonic microbiota and metabonome in a small group of gastrostomy fed children, who were either on an FD or BD, and compared, where possible to their siblings (17 FD, 28 BD, 19 HS). There was no increase in complications in tube blockage or infection rates, but a significant improvement in the prevalence of bowel problems, a reduction in medication and an increase in quality of life. Metataxonomic analysis showed that the FD group was significantly different to the Sibling group, and that families did not cluster together. Whole sample metabonomics showed no differences between groups; however, univariate analysis of biologically important metabolites did differ. Changing to a BD resulted in no increase in complications or risks, but improved the overall quality of life for the children and families.
Cancer-associated Mutations in Congenital Pulmonary Malformations: A Prospective Cohort
Authors: Simon Garinet, Makan Rahshenas, Louise Galmiche-Rolland, Olivier Abbo, Arnaud Bonnard, Frédéric Hameury, Naziha Khen-Dunlop, Babak Khoshnood, Hélène Blons, Christophe Delacourt, Sabah Boudjemaa, Laure Choupeaux, Sophie Collardeau-Frachon, Virginie Fouquet, Edouard Habonimana, Erik Hervieux, Nathalie Lelong, Guillaume Levard, Thierry Jo Molina, Cecile Picard, Christophe Piolat, Rony Sfeir, Florence Biquard, Jean-Paul Bory, François Goffinet, Valat-Rigot As, Norbert Winer, Eve Mousty, Charles Muszynski, Alexandra Benachi, Laurent J. Salomon, Valérie Goua, Jean-Marie Jouannic, Gwenaelle Le Bouar, Jérôme Massardier, Jonathan Rosenblatt, Agnès Sartor, Catherine Thong-Vanh, Fabienne Prieur, Thibaud Quibel, Claudine Touboul, Jean Gondry, Loic Sentilhes, Valérie Bonfiglioli, Lionel Carbillon, Anne-Helene Saliou, Julien Saada, Alexandra Letourneau, Helene Laurichesse, Carole Egron, Loren Deslandes, Vanina Castaigne, Claire Dazel-Salonne, Julien Stirnemann, Philippe Roth, Thierry Bultez, Yves Ville, Vassilis Tsatsaris, Lucie Guilbaud, Anne-Marie Darras, Jean-Francois Oury, Cecile Fanget, Romain Favre, Anne Paris, Franck Perrotin, Nathalie Banaszkiewicz, Thameur Rakza, Mathieu Morin, Cynthia Trastour, Nicolas Mottet, Frederic Coatleven, Elisabeth Alanio, Olivier Morel, Estelle Perdriolle, Marie-Laure Eszto-Cambon, Insaf Berrazaga, Guillaume Podevin, Hala Feghali, Caroline Thumerelle, Rafaelle Mangione, Marie-Noelle Lebras, Héloise Ducoin, Bernard Romeo, Philippe Buisson, Pierrick Cros, Léa Roditis, Hiline Devries, Jacques Brouard, Thierry Petit, Isabelle Petit, Adam Kandem Simo, Maguelonne Pons, Olivier Jaby, Catherine Llerena, Edith Sabatier, Guillaune Thouvenin, Michele Larroquet, Sabine Irtan, Christine Grapin, Caroline Parico, François Varlet, Jacqueline Matis, François Becmeur, Isabelle Gibertini, Hubert Lardy, Stephan Denapolicocci, Antoine Deschildre, Jean Breaud, Jean-François Lecompte, Arnaud Fotso Kamdem, Frédéric Elbaz, Frédéric Lavrand, Mickael Pomedio, Francis Lefebvre, Jean Louis Lemelle, Vladimir Gomola, Clementine Vigier, Isabelle Monier
Journal: American Journal of Respiratory and Critical Care Medicine (2022)
TCA-phospholipid-glycolysis targeted triple therapy effectively suppresses ATP production and tumor growth in glioblastoma
Authors: Shixue Yang, Jixing Zhao, Xiaoteng Cui, Qi Zhan, Kaikai Yi, Qixue Wang, Menglin Xiao, Yanli Tan, Biao Hong, Chuan Fang, Chunsheng Kang
Journal: Theranostics (2022)

Rationale: Glioblastoma (GBM) displays a complex metabolic reprogramming in cancer cells.Adenosine triphosphate (ATP) is one of the central mediators of cell metabolism and signaling.GBM cells generate ATP by glycolysis and the tricarboxylic acid (TCA) cycle associated with oxidative phosphorylation (OXPHOS) through the breaking-down of pyruvate or fatty acids to meet the growing energy demand of cancer cells.Therefore, it's urgent to develop novel treatments targeting energy metabolism to hinder tumor cell proliferation in GBM.Methods: Non-targeted metabolomic profiling analysis was utilized to evaluate cell metabolic reprogramming using a small molecule inhibitor (SMI) EPIC-0412 treatment.Cellular oxygen consumption rate (OCR) and the total proton efflux rate (PER), as well as ATP concentration, were tracked to study metabolic responses to specifically targeted inhibitors, including EPIC-0412, arachidonyl trifluoromethyl ketone (AACOCF3), and 2 deoxy-D-glucose (2-DG).Cancer cell proliferation was assessed by CCK-8 measurements and colony formation assay.Additionally, flow cytometry, immunoblotting (IB), and immunofluorescence (IF) analyses were performed with GBM cells to understand their tumorigenic properties under treatments.Finally, the anticancer effects of this combination therapy were evaluated in the GBM mouse model by convection-enhanced delivery (CED).Results: We found that SMI EPIC-0412 could effectively perturb the TCA cycle, which participated in the combination therapy of cytosolic phospholipase A2 (cPLA2)-inhibitor AACOCF3, and hexokinase II (HK2)-inhibitor 2-DG to disrupt the GBM energy metabolism for targeted metabolic treatments.ATP production was significantly declined in glioma cells when treated with monotherapy (EPIC-0412 or AACOCF3), dual therapy (EPIC-0412 + AACOCF3), or triple therapy (EPIC-0412 + AACOCF3 +2-DG) regimen.Our experiments revealed that these therapies hindered glioma cell proliferation and growth, leading to the reduction in ATP production and G0/G1 cell cycle arrest.We demonstrated that the combination therapy effectively extended the survival of cerebral tumor-bearing mice. Conclusion:Our findings indicate that the TCA-phospholipid-glycolysis metabolism axis can be blocked by specific inhibitors that significantly disrupt the tumor energy metabolism and suppress tumor Ivyspring
Testican-2 Is Associated with Reduced Risk of Incident ESKD
Authors: Donghai Wen, Linda Zhou, Zihe Zheng, Aditya Surapaneni, Christie M. Ballantyne, Ron C. Hoogeveen, Michael G. Shlipak, Sushrut S. Waikar, Ramachandran S. Vasan, Paul L. Kimmel, Ruth F. Dubin, Rajat Deo, Harold I. Feldman, Peter Ganz, Josef Coresh, Morgan E. Grams, Eugene P. Rhee
Journal: Journal of the American Society of Nephrology (2022)

Testican-2 was recently identified as a podocyte-derived protein that is released into circulation by the kidneys and is positively correlated with eGFR and eGFR slope. However, whether higher testican-2 levels are associated with lower risk of ESKD is unknown.
Identifying the E2F3-MEX3A-KLF4 signaling axis that sustains cancer cells in undifferentiated and proliferative state
Authors: Xu Yang, Guilin Li, Yuhua Tian, Xin Wang, Jiuzhi Xu, Ruiqi Liu, Min Deng, Chunlei Shao, Yuwei Pan, Xi Wu, Mengzhen Li, Chaowei Zhang, Rui Liu, Jun Qin, Chen Zhang, Zhanju Liu, Xin Wu, Maksim V. Plikus, Christopher J. Lengner, Zongheng Zheng, Cong Lv, Zhengquan Yu
Journal: Theranostics (2022)

Rationale: Dysregulation of signaling that governs self-renewal and differentiation of intestinal stem cells (ISCs) is a major cause of colorectal cancer (CRC) initiation and progression.Methods: qRT-PCR, western blotting, in situ hybridization, immunohistochemistry and immunofluorescence assays were used to detect the expression levels of MEX3A, KLF4 and E2F3 in CRC tissues.The biological functions of MEX3A were studied using Mex3a knockout (KO) and intestinal epithelium specific conditional knockout (cKO) mice, AOM-DSS mouse colorectal tumor model, Apc floxed mouse tumor model and intestinal and tumor organoids.Transcriptomic RNA sequencing (RNA-seq), RNA crosslinking immunoprecipitation (CLIP) and luciferase reporter assays were performed to explore the molecular mechanisms of MEX3A.Results: RNA-binding protein MEX3A, a specific ISC marker gene, becomes ectopically upregulated upon CRC and its levels negatively correlate with patient survival prognosis.MEX3A functions as an oncoprotein that retains cancer cells in undifferentiated and proliferative status and it enhances their radioresistance to DNA damage.Mechanistically, a rate limiting factor of cellular proliferation E2F3 induces MEX3A, which in turn activates WNT pathway by directly suppressing expression of its pro-differentiation transcription factor KLF4. Knockdown of MEX3A with siRNA or addition of KLF4 agonist significantly suppressed tumor growth both by increasing differentiation status of cancer cells and by suppressing their proliferation.Conclusions: It identifies E2F3-MEX3A-KLF4 axis as an essential coordinator of cancer stem cell self-renewal and differentiation, representing a potent new druggable target for cancer differentiation therapy.
Neuron(s)-on-a-Chip: A Review of the Design and Use of Microfluidic Systems for Neural Tissue Culture
Authors: David Choy Buentello, Mariana García-Corral, Grissel Trujillo-de Santiago, Mario Moisés Alvarez
Journal: IEEE Reviews in Biomedical Engineering (2022)

Neuron-on-chip (NoC) systems-microfluidic devices in which neurons are cultured-have become a promising alternative to replace or minimize the use of animal models and have greatly facilitated in vitro research. Here, we review and discuss current developments in neuron-on-chip platforms, with a particular emphasis on existing biological models, culturing techniques, biomaterials, and topologies. We also discuss how the architecture, flow, and gradients affect neuronal growth, differentiation, and development. Finally, we discuss some of the most recent applications of NoCs in fundamental research (i.e., studies on the effects of electrical, mechanical/topological, or chemical stimuli) and in disease modeling.
ESPNIC clinical practice guidelines: intravenous maintenance fluid therapy in acute and critically ill children— a systematic review and meta-analysis
Authors: David W. Brossier, Lyvonne N. Tume, Anais R. Briant, Corinne Jotterand Chaparro, Clémence Moullet, Shancy Rooze, Sascha C. A. T. Verbruggen, Luise V. Marino, Fahad Alsohime, Sophie Beldjilali, Fabrizio Chiusolo, Leonardo Costa, Capucine Didier, Stavroula Ilia, Nyandat L. Joram, Martin C. J. Kneyber, Eva Kühlwein, Jorge Lopez, Jesus López-Herce, Huw F. Mayberry, Fortesa Mehmeti, Magdalena Mierzewska-Schmidt, Maria Miñambres Rodríguez, Claire Morice, John V. Pappachan, Florence Porcheret, Leonor Reis Boto, Luregn J. Schlapbach, Hakan Tekguc, Konstantinos Tziouvas, Jean-Jacques Parienti, Isabelle Goyer, Frederic V. Valla
Journal: Intensive Care Medicine (2022)

Intravenous maintenance fluid therapy (IV-MFT) prescribing in acute and critically ill children is very variable among pediatric health care professionals. In order to provide up to date IV-MFT guidelines, the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) undertook a systematic review to answer the following five main questions about IV-MFT: (i) the indications for use (ii) the role of isotonic fluid (iii) the role of balanced solutions (iv) IV fluid composition (calcium, magnesium, potassium, glucose and micronutrients) and v) and the optimal amount of fluid. A multidisciplinary expert group within ESPNIC conducted this systematic review using the Scottish Intercollegiate Guidelines Network (SIGN) grading method. Five databases were searched for studies that answered these questions, in acute and critically children (from 37 weeks gestational age to 18 years), published until November 2020. The quality of evidence and risk of bias were assessed, and meta-analyses were undertaken when appropriate. A series of recommendations was derived and voted on by the expert group to achieve consensus through two voting rounds. 56 papers met the inclusion criteria, and 16 recommendations were produced. Outcome reporting was inconsistent among studies. Recommendations generated were based on a heterogeneous level of evidence, but consensus within the expert group was high. “Strong consensus” was reached for 11/16 (69%) and “consensus” for 5/16 (31%) of the recommendations. Key recommendations are to use isotonic balanced solutions providing glucose to restrict IV-MFT infusion volumes in most hospitalized children and to regularly monitor plasma electrolyte levels, serum glucose and fluid balance.
Divergent clonal differentiation trajectories of T cell exhaustion
Authors: Bence Daniel, Kathryn E. Yost, Sunnie Hsiung, Katalin Sandor, Yu Xia, Yanyan Qi, Kamir J. Hiam-Galvez, Mollie Black, Colin J. Raposo, Quanming Shi, Stefanie L. Meier, Julia A. Belk, Josephine R. Giles, E. John Wherry, Howard Y. Chang, Takeshi Egawa, Ansuman T. Satpathy
Journal: Nature Immunology (2022)
Ventilation Scintigraphy With Radiolabeled Carbon Nanoparticulate Aerosol (Technegas)
Authors: Pierre-Yves Le Roux, Wolfgang M. Schafer, Frédérique Blanc-Beguin, Mark Tulchinsky
Journal: Clinical Nuclear Medicine (2022)

Invented and first approved for clinical use in Australia 36 years ago, Technegas is the technology that enabled ventilation scintigraphy with 99m Tc-labeled carbon nanoparticles ( 99m Tc-CNP). The US Food and Drug Administration (FDA) has considered this technology for more than 30 years but only now is getting close to approving it. Meanwhile, more than 4.4 million patients benefited from this technology in 64 countries worldwide. The primary application of 99m Tc-CNP ventilation imaging is the diagnostic evaluation for suspicion of pulmonary embolism using ventilation-perfusion quotient (V/Q) imaging. Because of 99m Tc-CNP's long pulmonary residence, tomographic imaging emerged as the preferred V/Q methodology. The FDA-approved ventilation imaging agents are primarily suitable for planar imaging, which is less sensitive. After the FDA approval of Technegas, the US practice will likely shift to tomographic V/Q. The 99m Tc-CNP use is of particular interest in the COVID-19 pandemic because it offers an option of a dry radioaerosol that takes approximately only 3 to 5 tidal breaths, allowing the shortest exposure to and contact with possibly infected patients. Indeed, countries where 99m Tc-CNP was approved for clinical use continued using it throughout the COVID-19 pandemic without known negative viral transmission consequences. Conversely, the ventilation imaging was halted in most US facilities from the beginning of the pandemic. This review is intended to familiarize the US clinical nuclear medicine community with the basic science of 99m Tc-CNP ventilation imaging and its clinical applications, including common artifacts and interpretation criteria for tomographic V/Q imaging for pulmonary embolism.
A sporadic Alzheimer's blood-brain barrier model for developing ultrasound-mediated delivery of Aducanumab and anti-Tau antibodies
Authors: Joanna M. Wasielewska, Juliana C. S. Chaves, Rebecca L. Johnston, Laura A. Milton, Damián Hernández, Liyu Chen, Jae Song, Wendy Lee, Gerhard Leinenga, Rebecca M. Nisbet, Alice Pébay, Jürgen Götz, Anthony R. White, Lotta E. Oikari
Journal: Theranostics (2022)

Rationale:The blood-brain barrier (BBB) is a major impediment to therapeutic intracranial drug delivery for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD).Focused ultrasound applied together with microbubbles (FUS +MB ) is a novel technique to transiently open the BBB and increase drug delivery.Evidence suggests that FUS +MB is safe, however, the effects of FUS +MB on human BBB cells, especially in the context of AD, remain sparsely investigated.In addition, there currently are no cell platforms to test for FUS +MB -mediated drug delivery.Methods: Here we generated BBB cells (induced brain endothelial-like cells (iBECs) and astrocytes (iAstrocytes)) from apolipoprotein E gene allele E4 (APOE4, high sporadic AD risk) and allele E3 (APOE3, lower AD risk) carrying patient-derived induced pluripotent stem cells (iPSCs).We established mono-and co-culture models of human sporadic AD and control BBB cells to investigate the effects of FUS +MB on BBB cell phenotype and to screen for the delivery of two potentially therapeutic AD antibodies, an Aducanumab-analogue (Aduhelm TM ; anti-amyloid-β) and a novel anti-Tau antibody, RNF5.We then developed a novel hydrogel-based 2.5D BBB model as a step towards a more physiologically relevant FUS +MB drug delivery platform.Results: When compared to untreated cells, the delivery of Aducanumab-analogue and RNF5 was significantly increased (up to 1.73 fold), across the Transwell-based BBB models following FUS +MB treatment.Our results also demonstrated the safety of FUS +MB indicated by minimal changes in iBEC transcriptome as well as little or no changes in iBEC or iAstrocyte viability and inflammatory responses within the first 24 h post FUS +MB .Furthermore, we demonstrated successful iBEC barrier formation in our novel 2.5D hydrogel-based BBB model with significantly increased delivery (1.4 fold) of Aducanumab-analogue following FUS +MB .Conclusion: Our results demonstrate a robust and reproducible approach to utilize patient cells for FUS +MB -mediated drug delivery screening in vitro.With such a cell platform for FUS +MB research previously not reported, it has the potential to identify novel FUS +MB -deliverable drugs as well as screen for cell-and patient-specific effects of FUS +MB , accelerating the use of FUS +MB as a therapeutic modality in AD.